As early as 1937, it was observed that certain organic materials fluoresced following excitation from external sources. Approximately 10 years later, it was demonstrated that radioactive sources could induce scintillations in aromatic solvents that contained certain solutes. These early beginnings of “liquid scintillation counting” led to rapid advances in counting instrumentation (most notably the coincidence method) and to the development of scintillation “cocktails”. Many of the solvent-fluor combinations developed during the early work on scintillation cocktails are still in use today. Since most of the efficient fluors were non-polar, organic aromatic compounds, the primary solvents used to solubilize the fluors were also non-polar and aromatic. Further desirable properties such as high energy transfer capabilities and favorable chemical characteristics (freezing, boiling and flash points) led to the use of toluene and xylenes as the most widely employed primary solvents in scintillation cocktails.
The counting of aqueous samples containing β−-emitting radionuclides presented challenges in the development of suitable cocktails. Two approaches to overcoming the immiscibility of the aqueous samples and the organic cocktail solvents were studied. The initial approach involved dispersing organic fluor molecules in an aqueous solution that could be easily mixed with the aqueous sample to be counted. An examination of this approach reveals that several strategies for dispersing fluors were attempted and that some success was achieved.
Steinberg described a scintillation counting system in which a finely divided fluor, e.g. anthracene crystals, was dispersed in an aqueous solution (Steinberg. D. Radioassay of carbon-14 in aqueous solutions using a liquid scintillation spectrometer. Nature. 182:740-741, 1958) By achieving intimate contact between the sample and the fluor, many problems related to insolubility of the sample in organic solvents or to chemical quenching were eliminated. Myers and Brush reported the use of blue-violet grade anthracene particles coated with detergents as efficient systems for counting aqueous samples (Myers. L. S. Brush. A. H. Counting of alpha and beta radiation in aqueous solutions by the detergent-anthracene scintillation method. Analyt. Chem. 34:342-245, 1962) Work was also carried out in which a product known as “Pilot B” was employed; this product was composed of a polyvinyltoluene host containing p-terphenyl and diphenylstilbene as fluors (Harrah, L. A., Powell, R. C. Dose rate saturation in plastic scintillators. In: Organic Scintillators and Liquid Scintillation Counting. Ed. D. L. Horrocks and C. T. Peng. Academic Press. New York. p. 266, 1971) Either beads or filaments of Pilot B were packed into vials and covered with aqueous solutions containing β−-emitting radionuclides. Reasonable counting efficiencies were obtained with these systems. Detectors containing suspended scintillators ultimately found usefulness in flow-through cells used to detect β−-emitting radionuclides in liquid chromatography effluents (Schram, E. Flow-monitoring of aqueous solutions containing weak β− emitters. In: The Current Status of Liquid Scintillation Counting. Ed. E. D. Bransome. Grune and Stratton. New York. pp. 95-109. 1970) Finally, a system employing the formation of micellar suspensions for scintillation counting was reported by Ewer, M. J., Harding, N. G. L. Micellar scintillators: A rational approach to the design of stable assay solvents for liquid scintillation counting. In: Liquid Scintillation Counting. Volume 3. Ed. M. A. Crook and P. Johnson. Hevden & Son. London. pp. 220-233, 1974. The authors referred to work on micelles in aqueous systems, but ultimately settled on inverted micelles in organic solvents; in both cases, the fluors were located in the organic phase.
The disadvantages of these systems included maintaining the stability of the dispersion, and maintaining intimate contact between the radioactive sample and the fluor molecule. In addition, for some of these systems, it was evident that the addition of the aqueous radioactive sample could have untoward effects on the ability of the system to reliable quantify the amount of radioactivity in the sample. When the fluor molecule was protected from the samples, as in the case of filaments and modem flow-through cells, a distinct advantage was the marked reduction in chemical quenching, although optical quenching (self-quenching) was still a potential problem.
This approach was ultimately abandoned in favor of the alternative approach in which aqueous samples were mixed or solubilized in organic solvents into which fluors had been dissolved. Initially, this was accomplished by employing secondary solvents that were miscible with both water and toluene (e.g., alcohols, dioxane). Ultimately, a series of new surfactants were developed that allowed the emulsification of aqueous samples in organic cocktail solvents in sufficient quantities. This is still the basic technology employed when researchers use liquid scintillation counting to quantify the amount of radioactivity in aqueous samples. Commercially available cocktails may contain combinations of solvents, emulsifying agents and primary and secondary fluors. Although widely used, these cocktails have several shortcomings. Among these are that impurities in aqueous samples can lead to significant chemical and optical quenching; this can also occur as a result of the significant quantities of dissolved oxygen frequently found in aqueous samples. The emulsifying agents themselves can interact with fluor molecules resulting in significant quenching; the same can occur with solubilizing agents used to solubilize certain samples such as tissues or electrophoretic gels. Organic solvents and floors can interact with plastic scintillation vials producing wall effects. However, the greatest problem involves the disposal of the large quantities of “mixed” (radioactive and organic) waste generated by liquid scintillation counting. For example, a 1990 report commissioned by the Nuclear Regulatory Commission and the Environment Protection Agency titled “National Profile on Commercially Generated Low-Level Radioactive Mixed Waste” (NUREG/CR-5938) demonstrated the extent of the problem. Based on the report, 140,000 ft3 of mixed waste was generated by industry and academia in the United States in 1990 alone. Of this, approximately 100,000 ft3 or 71% was hazardous organic liquid scintillation fluid containing low-level long-lived mixed radioactive waste.
The most common fluor molecule used in organic-based cocktails is 2,5-diphenyloxazole (PPO), which is classified as “water-insoluble”. Further, PPO has the highest quantum yield (φ, 0.83) of the four primary fluor molecules shown in Table 1. For liquid scintillation counting, the optimal concentration of PPO dissolved in toluene or xylene is 5-7 mg/mL.
TABLE 1Characteristics of Scintillators Used inLiquid Scintillation CountingOptimumFluorescence[Flour]MaximumScintillatormg/mL(nm)Primary2,5-diphenyloxazole(PPO)5-73752,(4-biphenylyl)-5-phenyl-1,3,4-oxadiazole 8-10375(PBD)2-(4-biphenylyl)-5-(4-tert-butylphenyl)-1,3,4-12385oxadiaole butyl-PBD)2,5-bis(5-tert-butyl-2-benzoxazolyl)thiophene7446(BBOT)Secondary1,4-bis(5-phenyloxazol-2yl)benzene(POPOP)0.05-0.2 —1,4-bis(2-methylstyryl)benzene(bis-MSB)1.5—
U.S. Pat. No. 4,588,698 by Gruner et al. teaches the use of polyvinyltoluene microspheres containing solid phase scintillators that are coated with carbohydrate materials that provide a selective permeable coating for radioimmunoassay. A specific requirement is that the microspheres have a diameter of at least 1 micrometer (1000 nanometers), and more preferably have a “width at least as wide as the range of radioactivity of said radiation”. As a result of the selective permeable coating and the large size of the microspheres, the radiation detection system would be able to detect more diffusable lower molecular weight compounds with little or no interference from less diffusible higher molecular weight compounds. Gruner et al. do not teach the use of nanoparticles containing fluor molecules made from oil-in-water microemulsion precursors wherein said nanoparticles have diameters less than 100 nanometers and that are permanently suspended in an aqueous medium.
U.S. Pat. No. 5,512,753 by Thomson et al. describe the use of scintillator capsules wherein a liquid scintillator core is encapsulated within a shell made from a polymer such as melamine formaldehyde or polymethyl methacrylate. Thomson et al. teach the use of scintillator capsules having diameters from 0.1-10,000 micrometers made by “mechanical/physical processes or chemical processes” such as spray-coating, pan coating, fluid-bed coating, and interfacial polymerization or other chemical techniques that occur as an “emulsion or dispersion”. A preferred embodiment of the Thomson et al. invention is that greater than 99% of the scintillator core comprises aromatic liquid solvent(s) such as toluene or xylene that has dissolved primary fluor molecule in the range of 0.01 to 5.0% w/w and dissolved secondary fluor molecule in the range of 0.001 to 0.5% w/w. Thomson et al. do not teach the use of nanoparticles containing solid fluor molecules made from oil-in-water microemulsion precursors wherein said nanoparticles have diameters less than 100 nanometers and that are permanently suspended in an aqueous medium. Further, Thomson et al. do not teach the use of a system that is free of organic solvents. Finally, Thomson et al. do not the teach the use of a detection system that may comprise up to 33% w/w fluor molecule
U.S. Pat. No. 4,127,499 by Chen et al. describes the use of polymeric particles derived from a latex that are coated with at least one uniformly dispersed fluor wherein said latex particles have a diameter no greater than 0.2 micrometers. Chen et al. teaches the use of “substantially dry” systems wherein at least 80% by weight of water has been removed. Chen et al. further teach a method of preparing the fluor-coated latex particles by adding fluor molecule dissolved in a water-miscible solvent to latex particles with subsequent addition of water to force the fluor molecules into or onto the latex particles. Chen et al. further teach a method of coating the prepared system onto a solid support such as paper or film. Chen et al. do not teach the use of nanoparticles containing fluor molecules made from oil-in-water microemulsion precursors wherein said nanoparticles have diameters less than 100 nanometers and that are permanently suspended in an aqueous medium. Chen et al. further do not teach the use of nanoparticles containing high concentrations of fluor molecules that are formed in a one-step process and immediately useable.
U.S. Pat. No. 5,250,236 by Gasco describes the use of solid lipid microspheres that are formed by diluting one volume of the mixture of molten lipid substance, water, surfactant and possibly a co-surfactant to 100 volumes of cold water. Gasco teaches the preparation of microspheres smaller than one micrometer and in particular between 50-800 nanometers, and preferably between 100 and 400 nanometers. Gasco also teaches the preparation of microspheres wherein said solid lipid microspheres may contain a pharmacologically active substance, such as a drug. Gasco does not teach the use of nanoparticles containing fluor molecules made from oil-in-water microemulsion precursors wherein said nanoparticles are formed from oil-in-water microemulsions directly by cooling or by polymerization with no dilution of the most useful system.
As illustrated, the references described above appear to lack preferred compositions and properties for an effective and useful system to detect beta-particle emitting radioisotopes. Namely, the references do not describe or teach the use of oil-in-water microemulsion precursors wherein the oil-phase of the microemulsion contains high concentrations of fluor molecules; wherein said oil-in-water microemulsions are subsequently treated, or cured, to produce stable, permanently suspended nanoparticles having diameters less than 1000 nanometers, or even less than 100 nanometers. These useful nanoscintillation systems can be engineered in a one-step process and used to detect beta-particle emitting radioisotopes.